ADP-ribosylation factor6 regulates both [3H]-noradrenaline and [14C]-glutamate exocytosis through phosphatidylinositol 4,5-bisphosphate

Neurochemistry International
Q Zheng, J A Bobich

Abstract

GTP phosphohydrolase (cell regulating) (EC 3.6.1.47, ADP-ribosylation factor6, ARF6) has been shown to play an important role in different steps of membrane trafficking. It also regulates chromaffin granule exocytosis through phosphatidylcholine phosphatidohydrolase (EC 3.1.4.14, PLD) activation. In this study, the role of ARF6 in neurotransmitter release from both dense-core granules (DCGs) and synaptic vesicles (SVs) in rat brain cortex nerve endings was investigated. We observed that synaptosomal ARF6 is largely particulate but moves to a less easily pelleted compartment upon nerve ending stimulation. We also found that direct inhibition of ARF6 by a specific antibody or interference with ARF6 downstream effects by a myristoylated N-terminal ARF6 peptide both significantly decreased both [3H]-noradrenaline and [14C]-glutamate exocytosis. Addition of phosphatidic acid (PA) and phosphatidylinositol 4,5-bisphosphate (PIP2) partially or completely restored exocytosis. These findings suggest that ARF6 plays important regulatory roles for both DCG and SV exocytosis by activating PLD and ATP:1-phosphatidyl-1D-myo-inositol 4-phosphate 5-phosphotransferase (EC 2.7.1.68, PI4P-5K) to enhance PIP2 synthesis and nerve ending membrane tra...Continue Reading

Citations

Nov 11, 2005·Molecular Biology of the Cell·Olivera A JovanovicJulie G Donaldson
Jan 22, 2005·Journal of Neurochemistry·Qian ZhengAndreas Jeromin
Oct 27, 2009·Biochemical and Biophysical Research Communications·Eva-Maria GehringFlorian Lang
Oct 15, 2010·Journal of Cellular Physiology·Yuji FunakoshiYasunori Kanaho
May 22, 2007·Developmental Neurobiology·Gerald R V Hammond, Giampietro Schiavo
Feb 26, 2015·The Journal of Biological Chemistry·Leonardo E PelletánSilvia A Belmonte
Sep 20, 2011·Journal of Cellular Biochemistry·Anna V KnizhnikElena M Tchevkina

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